SMALL-INTESTINAL ABSORPTION OF BROPIRIMINE IN RATS AND EFFECT OF BILE-SALT ON THE ABSORPTION

The intestinal absorption characteristics of a poorly water-soluble dr ug, bropirimine, were investigated by the in-situ small intestinal loo p method using male Sprague-Dawley rats. Bropirimine in solution was w ell absorbed in the overall small intestine, following first-order kin etics. The rate determining step for the disappearance of bropirimine from the small intestinal loop after dosing in the suspension was the dissolution process from suspension. Bropirimine was:solubilized by so dium glycocholate. The disappearance of bropirimine from the small int estinal loop was suppressed by sodium glycocholate contained in the so lution, because of the loss of thermodynamic activity of bropirimine a fter its involvement in the micellar complex, not by the direct effect of bile salt on the permeability of intestinal mucosa. The disappeara nce of bropirimine was also suppressed by sodium glycocholate containe d in the suspension. The suppression by sodium glycocholate seemed to be caused by the greater influence of sodium glycocholate on the therm odynamic activity of bropirimine than on the dissolution from suspensi on.